Src transduces erythropoietin-induced differentiation signals through phosphatidylinositol 3-kinase.
EMBO J
; 20(20): 5666-77, 2001 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-11598010
ABSTRACT
In this study, we examined the molecular mechanism of erythropoietin-initiated signal transduction of erythroid differentiation through Src and phosphatidylinositol 3-kinase (PI3-kinase). Antisense oligonucleotides against src but not lyn inhibited the formation of erythropoietin-dependent colonies derived from human bone marrow cells and erythropoietin-induced differentiation of K562 human erythroleukaemia cells. Antisense p85alpha oligonucleotide or LY294002, a selective inhibitor of PI3-kinase, independently inhibited the formation of erythropoietin-dependent colonies. In K562 cells, Src associated with PI3-kinase in response to erythropoietin. Antisense src RNA expression in K562 cells inhibited the erythropoietin-induced activation of PI3-kinase and its association with erythropoietin receptor. PP1, a selective inhibitor of the Src family, reduced erythropoietin-induced tyrosine phosphorylation of erythropoietin receptor and its association with PI3-kinase in F-36P human erythroleukaemia cells. The coexpression experiments and in vitro kinase assay further demonstrated that Src directly tyrosine-phosphorylated erythropoietin receptor, and associated with PI3-kinase. In vitro binding experiments proved that glutathione S-transferase-p85alpha N- or C-terminal SH2 domains independently bound to erythropoietin receptor, which was tyrosine-phosphorylated by Src. Taken together, Src transduces the erythropoietin-induced erythroid differentiation signals by regulating PI3-kinase activity.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Células Precursoras Eritroides
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Proteínas Proto-Oncogénicas pp60(c-src)
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Eritropoyetina
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Receptores de Eritropoyetina
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Fosfatidilinositol 3-Quinasas
Límite:
Animals
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Humans
Idioma:
En
Revista:
EMBO J
Año:
2001
Tipo del documento:
Article
País de afiliación:
Japón